Stable, non-corrosive formulations for pressurized metered dose inhalers

Abstract

Pharmaceutical pressurized metered dosing inhalers (MDIs) are disclosed containing at least one dissolved halide substance, a suspended drug substance and a co-solvent, stabilized chemically and also against metal corrosion by the addition of an acid, an unsaturated suspending agent and water.

1 . A corrosion-resistant, pharmaceutically-stable pressurized metered dose inhaler composition comprising:
 at least one suspended pharmaceutical active ingredient   at least one dissolved pharmaceutical active ingredient   a dissolved halide   at least one co-solvent   at least one propellant   water in the range 0.1 to 10% w/w, and   an organic acid in the range 0.0001 to 0.01% w/w.   
     
     
         2 . The composition of  claim 1  wherein said halide comes from said pharmaceutical active ingredients. 
     
     
         3 . The composition of  claim 1  wherein said organic acid is replaced by a mineral acid in the range 0.000001 to 0.01% w/w. 
     
     
         4 . The composition of  claim 1  wherein said composition additionally contains a mineral acid in the range 0.000001 to 0.01% w/w. 
     
     
         5 . The composition of  claim 1  wherein said composition is packaged in cans fitted with a metering valve delivering between 20 and 200 microliters of said composition per shot. 
     
     
         6 . The composition of  claim 1  wherein said composition is packaged in cans made of materials selected from a group comprising AISI 316L stainless steel, uncoated aluminum alloy and coated aluminum alloy. 
     
     
         7 . The composition of  claim 1  wherein said dissolved pharmaceutical active ingredient is selected from a group consisting of Fenoterol Hydrobromide, Ipratropium Bromide, Oxitropium Bromide, Tiotropium Bromide, and Formoterol Fumarate. 
     
     
         8 . The composition of  claim 1  wherein said suspended pharmaceutical active ingredient is selected from a group consisting of Salbutamol Sulfate, R-Salbutamol Sulfate, Budesonide, Ciclosonide, Fluticasone Propionate, Fluticasone Fumarate, Salmeterol Xinafoate, and Formoterol Fumarate. 
     
     
         9 . The composition of  claim 1  wherein said suspended pharmaceutical active ingredient is Salbutamol Sulfate and dissolved pharmaceutical active ingredient is Ipratropium Bromide Monohydrate. 
     
     
         10 . The composition of  claim 1  wherein said co-solvent is ethanol or isopropanol. 
     
     
         11 . The composition of  claim 1  wherein said propellant is selected from a group consisting of fluorinated hydrocarbons HFA 134a, HFA 227ea and a mixture thereof. 
     
     
         12 . The composition of  claim 1  wherein said propellant is a hydrocarbon. 
     
     
         13 . The composition of  claim 1  wherein said propellant is a mixture of said hydrocarbon and said fluorinated hydrocarbon. 
     
     
         14 . A method of stabilizing corrosive metered dose inhaler formulations comprising addition of an optimal amount of an unsaturated suspending agent and an amount of water in the range 0.1% w/w to 10% w/w. 
     
     
         15 . The method of  claim 14  wherein said formulation is stable for at least six months at 40° C./75% RH storage condition and 2 years at 30° C./75% RH storage condition.